1. Field of the Invention
The present invention relates to a class of compounds generally known as chromogenic cryptahemispherands useful in the measurement of ions and more particularly, to a process for the preparation of such chromogenic cryptahemispherands.
2. Description of the Prior Art
Certain terms used in the present discussion should be defined to assure that the reader is of the same mind as the author as to their respective meanings. Thus the following definitions are provided to clarify the scope of the present invention.
The term "ionophore" includes, broadly, molecules capable of forming a complex with an ion in solution. For example, the cyclic polypeptide, valinomycin, binds selectively to potassium ions in solution to form a cationic complex. Also included in this term are podands, corands, cryptands, hemispherands, cryptahemispherands and spherands.
A "podand" is an organic linear compound containing donor or receptor atoms which has the capacity of associating with positively charged ions to form complexes.
The term "corands" refers to monocyclic compounds which contain electron donor atoms or acceptor atoms, which are electron rich or deficient, and which are capable of complexing with particular cations or anions because of their unique structures. Because of the unique sizes and geometries of particular corands, they are adaptable to complexing with various ions. In so complexing, the electron rich atoms, such as the oxygens in a corand, become spacially oriented towards the electron deficient cation. The carbon atom segments of the cycle are simultaneously projected in a direction outwards from the ion. Thus, the resultant complex is hydrophilic in the center, but is relatively hydrophobic at its perimeter.
"Cryptands" refers to polycyclic analogs of the corands. Accordingly, they include bicyclic and tricyclic multidentate compounds. In the cryptands, the cyclic arrangements of donor atoms is three dimensional in space, as opposed to the substantially planar configuration of the corands. A cryptand is capable of virtually enveloping the ion in three dimensional fashion and, hence, is capable of strong bonds to the ions in forming the complex. As with the corands, the donor atoms can include such atoms as oxygen, nitrogen and sulfur. The term "hemispherands" refers to macrocyclic or macropolycyclic ionophore systems, whose cavities are partially preorganized for binding by the rigidity of the hydrocarbon support structure and the spatial and orientational dictates of appended groups.
The designation "cryptahemispherand" was given by Donald J. Cram in 1986 (Cram, et al., J. Am. Chem. Soc., 108 pp. 2998-3005 (1986)) to the class of macrobicyclic compounds which show an extraordinary propensity for complexation of alkali metal cations. Cryptahemispherands combine the partially preorganized cavity features of the hemispherands, but contain multiple other ligand-gathering features of the cryptands. The generic structure of a cryptahemispherand is depicted, infra, as structure (I). ##STR2## wherein: R is hydrogen, alkyl, alkylidene, alkenyl, allyl, aryl or benzyle;
m is 0 to about 2; and PA1 n is 0 to about 2; PA1 R', same or different, is lower alkyl, lower alkylidene, lower alkenyl, allyl, aryl or benzyl; PA1 R", same or different, is hydrogen, lower alkyl, lower alkylidene, lower alkenyl, allyl, aryl or benzyl; PA1 Z is halogen; PA1 Y is an electron withdrawing group, e.g., CN, NO.sub.2, CF.sub.3, COOR; PA1 m is 1 to 3; PA1 n is 1 to 3; PA1 a is 1 to 3; PA1 b is 1 to 3; PA1 k is 1 to 3; PA1 l is 1 to 3; and PA1 x is 2 to 4.
Certain compounds were described in the literature prior to Cram, et al. supra, which are capable of not only behaving as ionophores by forming cation complexes, but also, when complexed, exhibit a detectable formation of or change in color.
Thus, experiments were published in 1977 whereby chromogenic moieties were covalently attached to ionophores to achieve a color change response to potassium (Takagi, et al., Analytical Letters, 10(3), pp. 1115-1122 (1977)). There it is taught to couple covalently a chromogenic moiety such as 4-picrylamino to an ionophore such as benzo-15-corand-5. Moreover, U.S. Pat. No. 4,367,072 mentions many corands, cryptands and podands covalently substituted with a chromogenic group, such as ##STR3##
Yet another reference, German Offenlegungschift No. 3202779, published Aug. 4, 1983 discloses a chromogenic cryptand structure.
Although the synthesis of non-chromogenic cryptahemispherands have been described by Cram, et al., incorporation of a chromogenic moiety into the cryptahemispherand structure requires different synthetic strategy and has not been described before.